The hepatitis B virion (HBV), also known as the Dane particle, is a 42 nm complex spherical particle composed of an outer lipoprotein coat (Hepatitis B surface antigen, HBsAg) and an inner core (Hepatitis B core antigen, HBcAG). This core contains a circular partially double stranded DNA and a DNA polymerase. In vitro, the DNA polymerase fills in a large single stranded region in the genome, generating a fully double stranded region in the genome, generating a fully double stranded DNA.
So far, the nature of the Dane particles associated DNA polymerase remains uncertain. Selective inhibition of the HBV DNA polymerase by intercalating agents, pyrophosphate analogs, and arabinofuranosyl nucleotides is known and offers the ability to inhibit hepatitis B virus replication in individuals suffering from chronic hepatitis B. The present invention is concerned with the inhibition of HBV DNA polymerase in vivo by 5-substituted-1-(2'-deoxy-2'-substituted-beta-D-arabinofuranosyl compounds, previously known as anti-herpesvirus agents, as reported in U.S. Pat. No. 4,211,773 to Lopez et al.
An agent very closely related to HBV is known in woodchucks: the woodchuck hepatitis virus (WHV). Both agents belong to the same new class of viruses, sometime designated Hepa-DNA viruses. As previously suggested, HBV and WHV DNA polymerases do share the same basic features. The WHV DNA polymerase activity was therefore studied in parallel with that of HBV in the initial in vitro work described below.